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 Table of Contents  
META-ANALYSIS
Year : 2018  |  Volume : 2  |  Issue : 2  |  Page : 37-44

Infertility in the Middle East and North Africa Region: A systematic review with meta-Analysis of prevalence surveys


School of Clinical and Applied Sciences, Leeds Beckett University, Leeds, England, UK

Date of Web Publication29-Jun-2018

Correspondence Address:
Dr. Abdallah Eldib
School of Clinical and Applied Sciences, Leeds Beckett University, Leeds, England
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/LJMS.LJMS_24_18

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  Abstract 


Infertility is a worldwide health issue with high impact on the individuals involved and the society as a whole. Estimates of infertility are very important to inform social and economic policies. The aim of this systematic literature review is to estimate the prevalence of primary and secondary infertility in Middle East and North Africa (MENA) region and produce the overall estimate of the different indicators of infertility in MENA region. A systematic search was conducted to identify publications providing data from MENA countries. All titles and abstracts retrieved using this search strategy were managed by Endnote software, duplicates were removed and studies on animals, systematic reviews, and from non-MENA region was removed from the EndNote library. Seven electronic databases and websites were searched for relevant articles and surveys with no language or date restriction on July 2017. Data of prevalence, risk factors, and causes of infertility were extracted from included articles and meta-analyzed to produce the overall effect sizes of the infertility estimates. Eight cross-sectional studies and one World Health Organization report contained the prevalence data from four MENA countries were included in this study. The clinical primary infertility defined as "the failure to become pregnant after 12 months or more of continuous and unprotected sexual intercourse" was estimated in 5 surveys as 3.8% (95% confidence interval (CI) = 1.7–8.4, effect size = −7.564, P = 0.0001), with the total clinical infertility, both primary and secondary infertility, estimate was 17.2% (95% CI = 10.6–26.7, effect size = −5.5, P = 0.0001). Demographic primary infertility was 22.6% (95% CI = 13.4–35.5, effect size = −3.8, P = 0.0001) and demographic total infertility rate was 38.5% (95% CI = 28.8–49.2, effect size = −2.11, P = 0.035). The data extracted suggested, overall, that clinical primary infertility is low at 3.8% and demographic infertility in MENA region is high, at 22.6%.

Keywords: Demographic definition, Middle East and North Africa region, primary infertility, secondary infertility


How to cite this article:
Eldib A, Tashani OA. Infertility in the Middle East and North Africa Region: A systematic review with meta-Analysis of prevalence surveys. Libyan J Med Sci 2018;2:37-44

How to cite this URL:
Eldib A, Tashani OA. Infertility in the Middle East and North Africa Region: A systematic review with meta-Analysis of prevalence surveys. Libyan J Med Sci [serial online] 2018 [cited 2018 Nov 16];2:37-44. Available from: http://www.ljmsonline.com/text.asp?2018/2/2/37/235693




  Introduction Top


Fertility is normally measured in terms of number of live children delivered by women of childbearing age, usually defined as 15–49 years of age, although births to women outside this age range can, and do, occur.[1] In a highly publicised report by the United Nations Department of Economic and Social Affairs population division, it was concluded that fertility, as measured by number of live births per woman, has declined in all regions with the exception of Europe in which the fertility increased by 0.2 (from 1.4 to 1.6) live birth per woman from 2000 to 2005 and 2010 to 2015. The decline in total fertility during the same period was from 5.1 to 4.7 in Africa, from 2.4 to 2.2 in Asia, and from 2.5 to 2.1 in Latin America and the Caribbean, and from 2.0 to 1.85 in Northern America, and there was little change in Oceania as the fertility stayed at 2.4.[2] Some academics and politicians warn that if this rate keeps falling, the world population will eventually stop growing and may actually start shrinking toward the end of the 21st century (Department of Economic and Social Affairs – UN).

However, birth rate and live birth rate as measure of fertility are poor indicators of infertility as defined by clinical and epidemiological research.[1] On the other hand, fertilization rate, implantation rate, and pregnancy rate are related clinical measures which have been used to assess infertility. However, they cannot be used interchangeably as they describe success at different stages of the life cycle of the embryo, fetus, and newborn babies.[3]

In general, infertility is defined as not being able to get pregnant (conceive) after 1 year or more of unprotected intercourse. Clinically, infertility is "a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse."[4] The World Health Organization (WHO's) epidemiologic definition of infertility increases the time for a chance of getting pregnant to 2 years "women of reproductive age (15–49 years) at risk of becoming pregnant (not pregnant, sexually active, not using contraception, and not lactating) who report trying unsuccessfully for a pregnancy for 2 years or more."[5] Demographical definition of infertility, which is widely used in international organizations surveys, is "an inability to become pregnant with a live birth, within 5 years of exposure based upon a consistent union status, lack of contraceptive use, nonlactating, and maintaining a desire for a child."[6]

Based on statistics from Europe, North America, and elsewhere, approximately 85% of couples will conceive within 1 year of unprotected intercourse and this number will increase to about 95% within 2 years if they have unprotected sex around the time of ovulation.[7] For couples who have been trying to conceive for more than 3 years without success, the likelihood of pregnancy occurring within the next year is 25% or less.[8]

Infertility impact on the well-being of affected individual and is of great demographic significance to inform future social, educational, and health planning. Research on, and data from, the developing countries, in general, and in the Middle East and North Africa (MENA) region, in particular, about infertility is lacking.[9] This is mainly because of poorly funded research and limited resources for different governmental and nongovernmental organizations but could also be due to the fact that peer-reviewed articles, surveys and reports about MENA health issues are mainly published in local languages and are hardly accessible through electronic databases and other internet-based resources. There is a need to search the literature extensively to have a reasonable estimate of infertility in MENA region. The aim of this systematic review is, therefore, to estimate the prevalence of primary and secondary infertility in MENA region.


  Methods Top


Search methods for identification of studies

In PubMed, a MeSh, which is the National Library of Medicine's controlled vocabulary thesaurus, based search was applied using the following search algorithm:

("Infertility" [Mesh] AND "Prevalence" [Mesh]) AND "Middle East" (Mesh)

In other databases, the search strategy combined keywords and terms of infertility prevalence and region as shown in [Table 1]. The search was designed to be broad to cover all relevant articles indexed in the different database. The Arabic equivalent of this strategy was applied in Google and Google Scholar.
Table 1: Search strategy to be applied to search for articles*

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All titles and abstracts retrieved using this search strategy were managed by Endnote software, duplicates were removed and studies on animals, systematic reviews, and from non-MENA region were also removed from the EndNote library.

Electronic searches

Five electronic databases (Science Direct, Web of knowledge, Medline, Embase, and Cinahl) were searched for relevant articles with no language or date restriction on July 2017. Further search using both English and Arabic language was carried out in Google scholar, Google, and the WHO website to identify further potential articles or surveys. Conference proceedings of the MENA Societies of Reproductive Health and Bibliographies from relevant articles were also handsearched by the two reviewers. Studies were included in this review if they contain infertility prevalence data based on cross-sectional studies on the general population in a MENA country and were published in a peer-reviewed journals or National Survey Reports collected by international or regional organizations.

The prevalence in this review refers to the proportion of couples or individuals who have infertility in a given sample, while incidence refers to how many new cases of infertility recorded per year. However, the primary outcomes of interest were prevalence, rather than incidence rate, of infertility. Therefore, the definition of infertility in this systematic review is the WHO's epidemiologic definition. The clinical definition which specifies 1 year only for unsuccessfully trying for a pregnancy was also used if studies have used this definition. If only demographic data were available, then the demographic definition of infertility was also used.

Risk factors such as age and whether the infertility was caused by a male or female factor or both or by unknown or unexplained factor were assigned as the secondary outcomes in this review. All titles identified were screened by the first reviewer then the two reviewers selected independently all potential abstracts. Full articles of the selected abstracts were retrieved and the two reviewers apply the full inclusion/exclusion criteria on the retrieved articles. Any dispute about the appropriateness of an article or a study was resolved by discussion and agreement between the two reviewers.

Quantitative data on infertility in MENA countries were extracted from surveys carried out by governmental departments and added on to the meta-analysis to estimate the different indicators of infertility in MENA region.

Inclusion and exclusion criteria

Published papers and reports, in any language, based on population-based studies with a random selection of a representative sample were included. While case reports and clinical studies, in which the sample is not representative of the population and may not contain prevalence data were excluded.

Data extraction and management

Prevalence data and sample characteristics were extracted and tabulated. Data on risks factors and treatments used and their success rate were also collected, if reported, and presented. Data were tabulated and differences between countries and with other regions of the world were examined.

Quality assessment of the study

The selected studies were assessed using criteria developed by Loney et al., for observational studies.[10] The quality criteria were scored as following: use of random sample or whole population, unbiased sampling frame, adequate sample size at least (600), use of known validated and tested tools, definition of infertility used, adequate response rate (70%), point prevalence estimates provided, reporting confidence interval (CI) or standard error, and description of study participants. After the quality assessment of the studies was recorded, studies were stratified according to the total score from 1 to 9. Studies were scored against 9 criteria and rated high quality if 7 or more criteria were met, medium if 5–6 criteria were met, and low if <5 criteria were met.

Assessment of heterogeneity and publication bias

By plotting a Forest plot and calculating the I2 of all the selected studies, it was possible to judge on the heterogeneity between the studies. Funnel plot and associated statistics were produced using comprehensive meta-analysis software to assess the publication bias.

Data synthesis

After data were described, prevalence data from each country in MENA region were pooled. This allowed for an estimation of an overall prevalence. The meta-analysis results were then discussed in a narrative synthesis of data to investigate if the MENA region trend of infertility is different from the rest of the world. Comparing between countries of the MENA region was also carried out.


  Results Top


The electronic search revealed 481 hits. Further 6 articles and 1 WHO report were identified as potentially relevant manually from reference lists of other reviews and studies [Figure 1]. After 104 duplicates were removed, 384 titles and abstracts were screened independently by two reviewers and 362 were deemed irrelevant. This produced a final 22 studies and surveys. The full text of these articles and reports were scrutinized against the eligibility criteria and both reviewers agreed that 13 articles should be excluded.[6],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] The reasons for exclusion of these articles included data on MENA region was unavailable, being a discussion article, not a cross-sectional study, or a study of treatment of infertility [Table 2].
Figure 1: PRISMA 2009 Flow Diagram showing the selection process of the studies

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Table 2: The excluded studies with reasons

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Eight cross-sectional studies which were published in peer-reviewed journals were selected.[25],[26],[27],[28],[29],[30],[31],[32] In addition, one WHO report carried out within the Demographic and Health Surveys (DHS) program contained prevalence data from 4 MENA countries and thus was also included.[33] The quality of these 9 publications was assessed and data were extracted and tabulated.

Seven studies, including the DHS report, scored 7 or more on the quality assessment criteria, suggesting that they are of high quality. However, one limitation of these studies was the failure to describe the participants in adequate details. The remaining two studies scored 6 and 5 for failing to use unbiased sampling frame, describe the participants and provide CIs of the infertility rate, or a working definition of infertility.

Surprisingly, 7 out of 9 studies and surveys were conducted in Iran. The remaining research areas were Saudi Arabia in one peer-reviewed journal and Egypt, Morocco, Jordan, and Yemen survey reports in the DHS program. Five out of the 7 studies used the clinical definition of infertility by the American Society for Reproductive Medicine. In this definition, "infertility is referred to as the failure to become pregnant after 12 months or more of continuous and unprotected sexual intercourse." One study used the WHO, epidemiological, infertility definition "the woman has never conceived despite cohabitation and exposure to pregnancy for a period of 2 years," and it was unclear what definition was used in other two studies. In the report by DHS program primary infertility was defined, demographically, as "Percentage of women who have been married for the past 5 years, who have ever had sexual intercourse, who have not used contraception during the past 5 years, and who have not had any births" [Table 3], the term married in this report was used to refer to all women who were in formal and informal consensual unions. Secondary infertility was defined by this report as percentage of women with no births in the past 5 years but who have had a birth at some time while other studies define it as failure to conceive after one successful pregnancy.
Table 3: Quality assessment of the included studies

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Sample size of the 8 peer-reviewed studies selected was 5200 couples in one study and 30,074 women in the other 7 studies. This made up a sample size of 35,274 women. Out of this sample size, 5519 women (16%) were defined as infertile. Primary and secondary infertility was also investigated in all 8 studies and there were 1740 women (32% of infertile women) was diagnosed with primary infertility (5%), while 3779 women (68% of infertile women) had secondary infertility (11%). Male, female, both factors, and unexplained factors of infertility were estimated in 3 studies only.

In addition, 35,494 women were surveyed in Egypt, Jordan, Morocco, and Yemen and the DHS report found that 36.5% (n = 12,939) women of these 4 countries had total infertility. Percentage of primary infertility was 20.9% (n = 7405) and secondary infertility was 15.6% (n = 5534). There was no reporting on the causes of infertility in this publication [Table 4].
Table 4: Characteristics studies and surveys included

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As the studies and surveys used different definitions, we pooled the data of each definition together taking the weight of the sample size into consideration. However, heterogeneity was high as indicated by the value of I2 of 99%. Publication bias was also high as suggested by the uneven distribution of standard errors by logit event rates on the funnel plot. Forest plots, using the random effect size model, was produced [Figure 2] and [Figure 3] to estimate the overall primary and total clinical infertility of four studies from Iran and one study from Saudi Arabia.
Figure 2: Forest plot of five studies with estimates of primary infertility rates according to the clinical definition of infertility. This figure is showing an overall primary infertility rate of 3.8% (95% confidence interval = 1.7-8.4, effect size = −7.564, P = 0.0001)

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Figure 3: Forest plot of five studies with estimates of total infertility rate according to the clinical definition of infertility. This figure is showing an overall total infertility rate of 17.2% (95% confidence interval = 10.6–26.7, effect size = −5.5, P = 0.0001)

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According to the clinical definition of infertility, the estimation of the overall primary infertility rate for the forest plot of 5 studies (four surveys from Iran and one survey from Saudi Arabia) was 3.8% (95% CI = 1.7–8.4, effect size = −7.564, P = 0.0001) [Figure 2], and the estimation of the overall total infertility rate for the same 5 studies was 17.2% (95% CI = 10.6–26.7, effect size = −5.5, P = 0.0001), [Figure 3].

Using the demographic definition of infertility, the estimation of the overall primary infertility rate for the forest plot of four surveys (demographic surveys on Egypt, Morocco, Jordan, and Yemen which were reported by the WHO DHS program) was 22.6% (95% CI = 13.4–35.5. effect size = −3.8, P = 0.0001) [Figure 4], and the estimation of the overall total infertility rate for the same four surveys was 38.5% (95% CI = 28.8–49.2, effect size = −2.11, P = 0.035) [Figure 5]. Heterogeneity among the four surveys was also high I2 = 99% and visual inspection of the funnel plot indicated a publication bias.
Figure 4: Forest plot of four surveys using the demographic definition of infertility and showing an overall primary infertility rate of 22.6% (95% confidence interval = 13.4–35.5. effect size = −3.8, P = 0.0001)

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Figure 5: Forest plot of four surveys using the demographic definition of total infertility and showing an overall total infertility rate of 38.5% (95% confidence interval = 28.8–49.2, effect size = −2.11, P = 0.035)

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Factors causing infertility were reported in three studies from Iran.[25],[27],[30] Data were published as number and percent of the cause from the total of infertility in two studies and from primary infertility in one study [Table 5]. Male factor was the cause of infertility in almost 25% of infertile couples, while female factor contributed to almost half of all infertility (range 40%–58%). Both male and female factors of infertility were responsible for an average of 6% of all infertile couples. However, most variations were in the unexplained cause of infertility with the percentage of (9%, 34% and 15%).
Table 5: Classification of factors causing infertility in three surveys from Iran*

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  Discussion Top


There were clear differences in the definitions of infertility between studies published in peer-reviewed journals reported here and surveys in DHS report. The differences are of two folds:

  1. Failure to have a pregnancy (clinical or epidemiological definition) versus failure to have successful birth (demographic)
  2. One year (clinical) or 2 years (epidemiological) of infertility versus at least 5 years (demographic).


Moreover, most sample surveys include a relatively small number of women over age 40 and therefore, sampling errors are to be expected. Larsen and Menken have identified two further problems with some of the infecundity (infertility) measures that were used in the World Fertility Survey: The ages to which the measures refer to are not specified, and the sensitivity of the estimators to different age patterns of sterility is not tested.[34] This was very clear in the studies and surveys reviewed here. In addition, heterogeneity was high among all studies and there is a publication bias in favor of high rates of infertility.

All women were in formal and informal consensual unions with the exception of Morocco in which all women whether married, cohabitated, or not were included. Therefore, Morocco has the highest percentage of total infertility (56.8%) (95% CI 0.547–0.589) and has the highest percentage of primary infertility (44.3%) because the surveyors in Morocco, intentionally or not intentionally, included in their sample the highest proportions of sexually active women aged 15–19 years who have not had a pregnancy.[33] Morocco secondary infertility is not so different from other countries in the Middle East (12.5%).

Articles included from Iran in this systematic review were research publications and there were no surveys commissioned by international organizations available. This is in contrast to information about other countries, which were mostly from demographic surveys. Thus, a major finding of this systematic review is that there is a lack of scientific research in MENA region (other than Iran) on clinical infertility. This could be because of two main reasons: (1) social taboos and the reluctance of people affected to speak about infertility. This makes it difficult for researchers to conduct reviews and distribute questionnaires. (2) Lack of public and private funding for such research projects.

In DHS, infertility was defined as no live birth after 5 years of trying to get pregnant, which differs from the clinical definition of failure to conceive after 1 year. As far as, the demographic definition of infertility is concerned the prevalence figure which was provided to countries in the MENA region (with the exception of Iran) was very high at 33% (95% CI 0.326–0.337) compared with other regions in the world. The demographic infertility prevalence in other regions ranged from 13.7% to 25.7% in Sub-Saharan Africa, 12%–25.9% in Central Asia/South and Southeast Asia, and 10.5% to 25.8% in Latin America/Caribbean.[33]

This high demographic infertility rate is echoed in an analysis on globally provided total fertility rate (TFR) which is strongly correlated with demographic infertility. In this analysis, a trend was identified of TFR drop from 4.8 in 1970 to around 2.5 in 2010 in all world regions. The fertility rate data is reliable as it is provided by registry and census rather than surveys and it is very significant as the WHO, governmental, and nongovernmental organizations need the data to monitor growth of populations. However, it is essential to carry out new research on clinical infertility in the MENA regions as other indicators suggest that infertility as defined clinically and epidemiologically in this region is not as high as the demographic surveys indicate. Only three studies reported the causes of infertility as male, female, both, or unexplained factors with almost half of the causes are attributed to the female factor.

This systematic review with meta-analysis is the first review of infertility in the MENA region and provides point prevalence of infertility according to different definitions. However, our findings are limited by the lack of studies and surveys in most countries of the region and the lack of robust methodology in some of the surveys reported. The meta-analysis was conducted according to a random effect model, yet the high heterogeneity and publication bias among the studies and surveys is a matter of concern.


  Conclusions Top


In this systematic review, there was more research on one country than on all other countries combined in MENA region which makes any overall pooling of data biased to IRAN, and there are also different definitions of infertility. However, it can be concluded that the prevalence of infertility as defined in demographic surveys is extremely high possibly because of inclusion of many unmarried or cohabitated women, especially in Morocco. The data extracted suggested, overall, that clinical primary infertility is low at 3.8% and demographic infertility in MENA region is high, at 22.6%, but cast a shadow on the inclusion criteria during the WHO-led surveys.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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